Is there a common mechanism by which protein movement across capillaries is enhanced after a number of unrelated stimuli? We have reinvestigated the effects of hyperosmotic solutions on the blood-brain barrier (BBB) to horseradish peroxidase (HRP). We had previously found that the intracarotid infusion of 2.0 M urea solutions resulted in the penetration of HRP between tight junctions in cerebral endothelium. When 1.4 M arabinose is so infused in rats, the great majority of interjunctional clefts are not penetrated yet HRP is exuded from vessels. A second possible mechanism, vesicular transport, may be responsible for the exudation. We have eliminated this possibility by the following control experiment: The hyperosmotic solution is infused, the brain is fixed by aldehydes and then from 1 to 3 hours post-fixation, the HRP is infused into the aorta. Fixation eliminates vesicular transfer yet the pattern of exudates is very similar to that which developed in living animals and are confined to the side receiving the arabinose. The conclusion is that the HRP may have crossed via actively formed channels that remain patent long enough to be fixed in the open position or by actual injury and wide separation of a few endothelial cells. BIBLIOGRAPHIC REFERENCE: Brightman, M.W. and Robinson, J.S.: Some Attempts to Open the Blood-Brain Barrier to Protein. In McLaurin, R.L. (ed.): Head Injuries. New York, Grune & Stratton, 1976, pp. 107-113.